Macular Degeneration: D'Amico DJ

Regillo CD, D'Amico DJ, Mieler WF, Schneebaum C, Beasley CH, Sullins GT. · Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania 19107, USA. · Surv Ophthalmol. · Pubmed #17240259 No free full text.

Abstract: OBJECTIVES: Safety data for anecortave acetate 15 mg suspension (Retaane 15 mg, Alcon Research, Ltd., Ft. Worth, TX 76134) as primary or adjunctive therapy with photodynamic therapy are available for 358 patients with age-related macular degeneration who received this novel cortisene during clinical trials in which the drug was administered via posterior juxtascleral depot every 6 months for 2 years. METHODS: Detailed ophthalmic examinations, physical examinations, and adverse event reporting were used to characterize the clinical safety of anecortave acetate 15 mg and were monitored by an Independent Safety Committee. RESULTS: Anecortave acetate 15 mg was safe and well tolerated in the overall patient population. No serious, treatment-related deaths were reported. Ocular adverse events assessed as related to anecortave acetate 15 mg were non-serious with one exception (retinal detachment), mild to moderate in intensity with one exception, generally resolved with or without treatment, and did not interrupt patient participation in the studies with two exceptions. CONCLUSIONS: Anecortave acetate 15 mg is safe and well-tolerated when administered as a posterior juxtascleral depot at 6-month intervals for use as primary therapy or as adjunctive therapy with PDT.

Vavvas D, D'Amico DJ. · Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA. · Ophthalmol Clin North Am. · Pubmed #16935210 No free full text.

Abstract: Repeated Macugen intravitreal injections, well tolerated and safe when performed according to protocol, is the first successful pharmacotherapy for wet AMD. Macugen has already had a significant impact on neovascular AMD management, in regard to both individual patients with AMD lesions that would become amenable to treatment, and in its effects on visual function and its preservation in the aging United States population. Although results and delivery method are not optimal, the positive outcomes indicate the beginning, and not the limit, of pharmacotherapy for AMD. The benefits of Macugen therapy for AMD strongly outweigh the risks. It is pointed out by some that the overall magnitude of the efficacy results is very similar to the PDT trials and question why there is so much enthusiasm about a treatment that entails intravitreal injections every 6 weeks instead of PDT every 12 weeks. In all fairness, PDT is not equally efficacious across the lesion subtypes and sizes, whereas Macugen has effect with all lesion subtypes. In addition, these studies widen the armamentarium and open up the possibility of combination therapy in attacking neovascularization through multiple ways.

Christoforidis JB, D'Amico DJ. · Massachusetts Ear and Eye Infirmary, Boston 02114, USA. · Int Ophthalmol Clin. · Pubmed #14704528 No free full text.

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Ray S, D'Amico DJ. · Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. · Semin Ophthalmol. · Pubmed #12759847 No free full text.

Abstract: Cystoid macular edema (CME) following cataract surgery has been recognized for over 50 years as an important cause of suboptimal post-operative vision. The incidence of CME varies widely, but is likely in the range of 1-2% using modern cataract extraction techniques. The diagnosis of CME can generally be made on clinical examination with evidence of perifoveal cystic spaces and can be confirmed with use of fluorescein angiography to document the classic petaloid pattern of leakage mainly into the outer retina. Leak from perifoveal vessels is induced by inflammatory mediators and results in intraretinal fluid accumulation and corresponding decrease in retinal function. The risk factors most associated with CME; rupture of posterior capsule, vitreous loss, iris incarceration, use of iris fixated lenses, active uveitis and diabetes, may all increase the potency of these mediators and exacerbate post-operative CME. The treatment of CME remains controversial but generally starts with conservative observation in isolated angiographic cases and progresses through topical non-steroidal anti-inflammatory agents (NSAIDs), topical steroids, peri-ocular steroids, systemic steroids and surgical intervention in refractory cases. Even more controversial is the role of NSAID prophylaxis peri-operatively in preventing clinical CME. Though the data is tantalizing in the short term, there is little to support the long-term benefit of such prophylaxis with respect to visual outcomes.

Cunningham ET, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD, Anonymous00243. · Stanford University, USA. · Ophthalmology. · Pubmed #16154196 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME). DESIGN: Randomized, double-masked, multicenter, dose-ranging, controlled trial. PARTICIPANTS: Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks. INTERVENTION: Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36. MAIN OUTCOME MEASURES: Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36. RESULTS: One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss. CONCLUSIONS: In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.

Augustin AJ, D'Amico DJ, Mieler WF, Schneebaum C, Beasley C. · Eye Clinic, Städtisches Klinikum Karlsruhe, Moltkestrasse 90, 76133 Karlsruhe, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15290154 No free full text.

Abstract: BACKGROUND: Anecortave acetate is a synthetic derivative of cortisol, but very specific and irreversible chemical modifications to the cortisol structure have resulted in the creation of a potent inhibitor of blood vessel growth with no evidence non-clinically or clinically of glucocorticoid receptor-mediated bioactivity. The clinical safety of Anecortave Acetate administered as a posterior juxtascleral depot every 6 months for up to 4 years is reviewed in this manuscript. METHODS: Clinical safety and efficacy of the novel angiostatic agent Anecortave Acetate for Depot Suspension was evaluated in patients with subfoveal exudative age-related macular degeneration (AMD) in a masked, randomized, dose-duration clinical trial completed in June 2003. This safety and efficacy study enrolled and treated 128 patients at 18 clinical sites in the US and EU. This was the first clinical trial of Anecortave Acetate for Depot Suspension administered as a posterior juxtascleral depot. Assessments of clinical safety were made with general physical examinations including electrocardiograms and hematology/serum chemistry/urinalysis, detailed ophthalmic evaluations with fluorescein/indocyanine green angiography and assessments of best-corrected logMAR visual acuity. All safety reports have been reviewed periodically by an Independent Safety Committee responsible for overseeing these activities. RESULTS: No clinically relevant safety issues related to either Anecortave Acetate for Depot Suspension or the administration procedure have been identified by an Independent Safety Committee. The most frequent safety issues reported were cataractous changes, decreased visual acuity, ptosis, ocular pain, abnormal vision and subconjunctival hemorrhage, but the majority of these were assessed as unrelated to treatment. CONCLUSIONS: Anecortave Acetate for Depot Suspension (3, 15 and 30 mg) is clinically safe following administration and re-administration at 6-month intervals as a posterior juxtascleral depot using a specially designed curved cannula.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger DS, Luna SP, Robertson SM, Russell S, Singerman L, Slakter JS, Yannuzzi L, Zilliox P, Anonymous00262. · No affiliation provided · Ophthalmology. · Pubmed #14644721 No free full text.

Abstract: PURPOSE: To evaluate safety and efficacy of the angiostatic agent anecortave acetate, compared with a placebo, for treatment of subfoveal choroidal neovascularization (CNV). DESIGN: Ongoing masked, randomized, placebo-controlled, parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a placebo. PARTICIPANTS: There were 128 eyes of 128 patients with subfoveal CNV secondary to age-related macular degeneration who were enrolled and treated, with 80% (102/128) of eyes presenting with predominantly classic lesions at baseline. METHODS: All eyes received a posterior juxtascleral depot application of masked study medication or a placebo, with retreatment at 6-month intervals if the masked investigator believed the patient could benefit. Patients received periodic detailed ophthalmic examinations with both fluorescein and indocyanine green angiography, general physical examinations with electrocardiograms, and hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data were periodically reviewed by the Independent Safety Committee overseeing the study. MAIN OUTCOME MEASURES: Best-corrected logarithm of the minimum angle of resolution (logMAR) vision and fluorescein angiographic lesion characteristics were compared over time and among treatment groups. RESULTS: At month 12, anecortave acetate (15 mg) administered at 6-month intervals was statistically superior to the placebo for 3 measures of clinical efficacy: mean change from baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P = 0.0323), and prevention of severe vision loss (decrease of > or = 6 logMAR lines from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions revealed that anecortave acetate (15 mg) was also superior to the placebo at 1 year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and 0.0299, respectively). Anecortave acetate (15 mg) trended toward significance over the placebo at month 12 for inhibition of total lesion growth and for inhibition of both the total CNV component and the classic CNV component in both the overall and subgroup analyses. The Independent Safety Committee identified no clinically relevant treatment-related safety issues. CONCLUSIONS: Anecortave acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion growth.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM, Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P, Anonymous00326. · No affiliation provided · Retina. · Pubmed #12652226 No free full text.

Abstract: PURPOSE: To evaluate clinical safety and efficacy of the angiostatic agent anecortave acetate for treatment of subfoveal choroidal neovascularization secondary to AMD. METHODS: 128 patients were randomized to placebo treatment or one of three anecortave acetate doses. Study medication was administered as a posterior juxtascleral injection onto the posterior scleral surface. Best-corrected logMAR vision was obtained at baseline and follow-up visits. Fluorescein angiograms were evaluated for eligibility before enrollment and posttreatment. RESULTS: Six months after a single treatment, visual acuity (mean change from baseline logMAR values) was significantly better (P = 0.003) after anecortave acetate 15 mg than placebo. More patients treated with anecortave acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080), especially those with predominantly classic lesions (92% versus 65%, P = 0.021). Anecortave acetate 15 mg inhibited lesion growth significantly better than placebo (P = 0.001). Trends favoring the other doses over placebo were observed for vision preservation and lesion inhibition, but statistical significance was not achieved. The Independent Safety Committee overseeing this study identified no clinically relevant treatment-related changes. CONCLUSION: Anecortave acetate 15 mg is safe and effective for preserving or improving vision and for inhibiting lesion growth in patients with subfoveal AMD.

Anonymous00201, D'Amico DJ, Masonson HN, Patel M, Adamis AP, Cunningham ET, Guyer DR, Katz B. · Department of Ophthalmology, Harvard Medical School, Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. · Ophthalmology. · Pubmed #16647134 No free full text.

Abstract: OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD.

Slakter JS, Bochow TW, D'Amico DJ, Marks B, Jerdan J, Sullivan EK, Robertson SM, Slakter JS, Sullins G, Zilliox P, Anonymous00107. · Vitreous-Retina-Macula Consultants of New York, New York, New York, USA. · Ophthalmology. · Pubmed #16368146 No free full text.

Abstract: PURPOSE: To compare 1-year safety and efficacy of anecortave acetate 15 mg with photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT treatment. DESIGN: Prospective, masked, randomized, multicenter, parallel group, active control, noninferiority clinical trial. PARTICIPANTS: Five hundred thirty patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration were randomized to treatment with either anecortave acetate 15 mg or PDT. METHODS: In the anecortave acetate group, the drug was administered under the Tenon's capsule as a periocular posterior juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the first administration of anecortave acetate, patients in this treatment group received a sham PDT treatment, and sham PDT treatments were repeated every 3 months if there was evidence of leakage on fluorescein angiography (FA). Patients assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed based upon FA, and a sham PJD procedure at the beginning of the study and at month 6. Best-corrected visual acuity was determined at baseline and all follow-up visits. Safety data were regularly reviewed by an independent safety committee. MAIN OUTCOME MEASURE: Percent responders (patients losing <3 lines of vision) at month 12. RESULTS: Percent responders in the anecortave acetate and PDT groups were 45% and 49%, respectively (not statistically different, P = 0.43). The confidence interval (CI) for the difference ranged from -13.2% favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome for anecortave acetate was improved in patients for whom reflux was controlled and who were treated within the 6-month treatment window (57% vs. 49%; 95% CI, -4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse events related to the study drug were reported in either treatment group. CONCLUSIONS: The safety and efficacy outcomes in this study demonstrate that the benefits of anecortave acetate for the treatment of choroidal neovascularization outweigh the risks associated with either the drug or the PJD administration procedure.

Haimovici R, D'Amico DJ, Gragoudas ES, Sokol S, Anonymous00093. · Department of Ophthalmology, Boston University School of Medicine, DOB-10 720 Harrison Avenue, Boston, MA 02118, USA. · Ophthalmology. · Pubmed #11772599 No free full text.

Abstract: OBJECTIVE: To describe early and unusual features in 16 patients with deferoxamine-induced retinal toxicity and to assess the role of diagnostic tests in the diagnosis and management of patients with the disorder. DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixteen patients with deferoxamine retinopathy identified from members of the Vitreous, Retina, and Macula societies of the United States. INTERVENTION/TESTING: The patients underwent complete ophthalmologic examination. Most patients were also evaluated by fluorescein angiography and electrophysiologic testing. The diagnosis was based on the medical history, systemic and ocular findings, and the results of electrophysiologic tests. MAIN OUTCOME MEASURES: Ocular symptoms, ophthalmoscopic, fluoroangiographic, and electrophysiologic findings. RESULTS: We confirmed previously reported findings in patients with established disease, including macular and/or peripheral pigmentary changes, reduced electroretinographic (ERG) amplitudes, and reduced electrooculographic (EOG) light-peak to dark-trough ratios. Peripapillary, papillomacular, and paramacular patterns of retinal pigment epithelial (RPE) degeneration were each observed in one patient. Diffuse RPE or outer retinal fluorescence by fluorescein angiography was a marker for active retinopathy both at the onset of disease and during recurrence and preceded the development of RPE pigment mottling. CONCLUSIONS: Unusual patterns of deferoxamine retinopathy may occur in addition to the foveomacular and/or peripheral patterns previously described. Fluorescein angiography is particularly useful for determining whether there is ongoing retinal/RPE injury. ERG and EOG testing may indicate earlier or more widespread injury than is suggested by fundus examination alone. Patients who do not discontinue deferoxamine after the development of retinopathy risk further retinal/RPE injury and visual deterioration.

Zacks DN, Foster BS, D'Amico DJ. · No affiliation provided · Arch Ophthalmol. · Pubmed #10326974 No free full text.

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D'Amico DJ, Friberg TR. · No affiliation provided · Am J Ophthalmol. · Pubmed #11491094 No free full text.

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